Dobbs S M, Mawer G E, Rodgers M, Woodcock B G, Lucas S B
Br J Clin Pharmacol. 1976 Apr;3(2):231-7. doi: 10.1111/j.1365-2125.1976.tb00597.x.
A search for patient variables relevant to digoxin dose requirements was made in fourty-three patients with a wide range of renal and hepatic function. The daily dose of digoxin to achieve a mean serum concentration of 1.5 ng/ml, the standardized dose, was calculated for each patient. The standardized dose correlated significantly with the following variables, in descending order of correlation coefficient; creatinine clearance, serum creatinine concentration, body weight and serum albumin concentration. An equation containing the two independent variables, creatinine clearance and serum albumin concentration, had a significantly stronger correlation with standardized dose than creatinine clearance alone. Attempts were made in each patient to predict the standardized dose using both empirical prescribing methods and the published nomograms. Although a maximum of 70% of the variance of the standardized dose was explained, this corresponded approximately to one patient in three having a predicted dose outside the 95% confidnece limits for the standardized dose. There remain important sources of individual variation in digoxin dose requirements yet to be identified. Future application of empirical prescribing methods, such as multiple linear regression and Bayes' theorem, to prescription for large, defined patient groups may improve dose prediction for individual patients.
对43例具有广泛肾功能和肝功能的患者进行了与地高辛剂量需求相关的患者变量研究。计算出每位患者达到平均血清浓度1.5 ng/ml的地高辛每日剂量,即标准化剂量。标准化剂量与以下变量显著相关,按相关系数降序排列为:肌酐清除率、血清肌酐浓度、体重和血清白蛋白浓度。包含肌酐清除率和血清白蛋白浓度这两个独立变量的方程与标准化剂量的相关性明显强于单独的肌酐清除率。尝试对每位患者使用经验性处方方法和已发表的列线图来预测标准化剂量。尽管标准化剂量的最大70%的方差得到了解释,但这大约相当于每三名患者中有一名的预测剂量超出标准化剂量的95%置信限。地高辛剂量需求中仍存在尚未确定的重要个体差异来源。经验性处方方法,如多元线性回归和贝叶斯定理,未来应用于大型特定患者群体的处方可能会改善个体患者的剂量预测。